Reaction Steps
Prepared using General Procedure 19: To CDI (117 mg, 0.72 mmol) in DCM (1 mL) was added a suspension of (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 72 (150 mg, 0.36 mmol), Et3N (145 mg, 1.44 mmol) and DCM (1 mL) and the mixture stirred for 2 h at room temperature. The resulting solution was added to the preparative solution of pyrrolidine (77 mg, 1.08 mmol)) at room temperature. The reaction was stirred at room temperature for 16 h. The solvent was evaporated and the crude material was purified by preparative HPLC to afford 110 mg of (78%) of (R)-N-(4-(2-(3-cyano-4-isopropoxyphenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)pyrrolidine-1-carboxamide 172. LCMS-ESI (m/z) calculated for C27H28N4O2S: 472.1; found 473.2 [M+H]+, tR=3.79 min. 1H NMR (400 MHz, DMSO) δ 8.28 (d, J=2.3 Hz, 1H), 8.22 (dd, J=8.9, 2.4 Hz, 1H), 8.15 (s, 1H), 7.53 (d, J=7.3 Hz, 1H), 7.44 (d, J=9.1 Hz, 1H), 7.36-7.24 (m, 2H), 6.42 (d, J=8.6 Hz, 1H), 5.29 (q, J=8.4 Hz, 1H), 4.91 (hept, J=5.9 Hz, 1H), 3.31-3.20 (m, 4H), 3.17-2.95 (m, 2H), 2.43 (ddd, J=10.7, 6.2, 2.8 Hz, 1H), 2.00-1.87 (m, 1H), 1.87-1.72 (m, 4H), 1.37 (d, J=6.0 Hz, 6H); 13 C NMR (101 MHz, CDCl3) δ 164.79, 160.90, 156.46, 146.16, 141.10, 140.75, 137.75, 131.89, 131.80, 127.75, 127.71, 127.63, 126.53, 124.27, 115.92, 113.78, 103.60, 72.34, 55.78, 45.61, 34.87, 30.80, 25.57, 21.81.
